This invention relates to a method for continuously monitoring temperatures at multiple locations within a controlled temperature unit (CTU). The instant invention provides the advantage that the temperature probes used to acquire the data may be easily removed for good manufacturing practice (GMP) compliant calibration, and most importantly without disturbing the contents of the CTU.
CTUs are employed in a variety of applications. They are routinely used in stability studies as a part of drug development and manufacturing programs as well as storage of GMP raw materials, retain samples and bulk intermediates. Central to such programs is adherence to GMP requirements, which present an industry standard for manufacture. Compliance to good manufacturing practices requires regular calibration of CTUs to ensure proper operation of the unit.
Continuously monitored CTUs typically measure temperature by means of a thermocouple or RTD (Resistive Temperature Device). However, there is no commercially available CTU design which incorporates removable temperature sensor wiring or a thermocouple unit in order to provide both continuous acquisition and output of the data in a format able to be manipulated by computer software. The few CTUs that do have devices that output data to a computer are not able to be externally calibrated without disturbing the contents of the CTU or are only equipped to monitor a single heating or freezing element and not multiple locations within the CTU over the course of long term storage of samples. None of these CTUs has a removable RTD assembly to permit easy calibration. U.S. Pat. No. 4,776,705, discloses a device that permits the determination of temperature in hostile environments such as a high-temperature reactor. This device utilizes a removable thermocouple, however,the apparatus primarily addresses the problem of breakdown of the wires of the thermocouple due to interaction with the products of combustion of carbonaceous fuel. Similarly, U.S. Pat. No. 4,510,343 discloses a device to be used in petroleum cracking furnaces.
Both of these prior art devices are manufactured using a refractory material, typically a metal or ceramic, and neither of these devices has been employed in subfreezing conditions. These refractory materials maintain their integrity under high heats, but under freezing conditions, devices employing this construction run the risk of having the interior RTD freeze in place thereby effectively becoming irremovable. These devices have the potential for moisture accumulation as a result of incident air condensing on the RTD when it is removed from its seated position, resulting in freezing inside the thermowell.
In order to circumvent this problem, workers in the industry have resorted to inserting thermocouple wiring through the door gasket of a CTU requiring continuous observation. However, these wires must be removed from the CTU in order to calibrate them. Even careful removal of the wires, can lead to disruption of the contents of the CTU which, in addition to general inconvenience, may be fatal to long term stability studies requiring undisturbed incubation of samples for long periods of time. Replacement of the wires in identical locations is also difficult, and therefore a long-term assessment of temperature variation from a given probe is virtually impossible. The present invention solves this industry-wide problem.
Thus, the primary object of the instant invention is to provide a method for continuously monitoring temperature wherein the RTDs used in data acquisition may be easily removed for calibration without disturbing the contents of the CTU.